Dysregulation of mitophagy and mitochondrial homeostasis in cancer stem cells: Novel mechanism for anti-cancer stem cell-targeted cancer therapy

Despite the potential of cancer medicine, cancer stem cells (CSCs) associated with chemoresistance and disease recurrence are the significant challenges currently opposing the efficacy of available cancer treatment options. Mitochondrial dynamics involving the fission-fusion cycle and mitophagy are the major contributing factors to better adaptation, enabling CSCs to survive and grow better under tumour micro-environment-associated stress. Moreover, mitophagy is balanced with mitochondrial biogenesis to maintain mitochondrial homeostasis in CSCs, which are necessary for the growth and maintenance of CSCs and regulate metabolic switching from glycolysis to oxidative phosphorylation. In this review, we discuss different aspects of mitochondrial dynamics, mitophagy, and mitochondrial homeostasis and their effects on modulating CSCs behaviour during cancer development. Moreover, the efficacy of pharmacological targeting of these cellular processes using anti-CSC drugs in combination with currently available chemotherapeutic drugs improves the patient's survival of aggressive cancer types.

Automated summary

Mitochondrial dynamics and mitophagy play crucial roles in enabling cancer stem cells to adapt to the stressful tumor microenvironment, with maintaining mitochondrial homeostasis being essential for CSCs growth and metabolic switching. Targeting these cellular processes pharmacologically can improve patient survival in aggressive cancer types when combined with current chemotherapeutic drugs.